Theme 3:
Neoplasms I
Summary
1
,Content
Week 9: General principles of oncology and breast cancer....................................................................5
Oncological language..........................................................................................................................5
Curative..........................................................................................................................................5
Palliative.........................................................................................................................................5
Scoring the patient’s physical condition.........................................................................................5
Primary therapy..............................................................................................................................6
Adjuvant therapy............................................................................................................................6
Neoadjuvant therapy......................................................................................................................6
The hallmarks of cancer......................................................................................................................7
The normal cell cycle......................................................................................................................7
Self-sufficiency of growth...............................................................................................................7
Insensitivity to growth inhibition....................................................................................................8
Evasion of apoptosis.......................................................................................................................8
Unlimited replication......................................................................................................................8
Angiogenesis...................................................................................................................................8
Invasion and metastasis..................................................................................................................8
Deregulating cellular energetics.....................................................................................................9
Genomic instability.........................................................................................................................9
Avoiding immune destruction/tumour enabling inflammation......................................................9
Inflammation can stimulate tumour growth:.................................................................................9
Breast caner......................................................................................................................................10
Cancer diagnostics............................................................................................................................11
Clinical signs..................................................................................................................................11
Symptoms and diagnostics of breast cancer.....................................................................................12
Basic diagnostics...........................................................................................................................12
Symptoms of early breast cancer.................................................................................................12
Symptoms of advanced breast cancer..........................................................................................13
History taking................................................................................................................................14
Mammography.............................................................................................................................14
Ultrasound....................................................................................................................................15
MRI...............................................................................................................................................15
Chest X-ray vs CT scan..................................................................................................................16
Fine needle aspiration..................................................................................................................16
Core needle biopsy.......................................................................................................................17
2
, FDG-PET/CT..................................................................................................................................17
Breast cancer imaging: CT thorax/abdomen.................................................................................17
TNM and cancer staging...................................................................................................................19
TNM..............................................................................................................................................19
UICC staging..................................................................................................................................20
Cancer treatment.............................................................................................................................21
Surgery.........................................................................................................................................21
Radiotherapy................................................................................................................................21
Systemic therapy..........................................................................................................................22
Chemotherapy..............................................................................................................................23
Immunotherapy............................................................................................................................24
Hormonal therapy........................................................................................................................24
PARP inhibitors:............................................................................................................................24
Follow-up and aftercare...................................................................................................................24
Palliative treatment and care...........................................................................................................27
Statistics...........................................................................................................................................28
Risk...................................................................................................................................................29
Case 1:..........................................................................................................................................29
Case 2:..........................................................................................................................................30
Bayesian thinking..........................................................................................................................30
Week 10: Fever, bleeding and fatigue..................................................................................................31
Haematopoiesis................................................................................................................................31
Leukaemia........................................................................................................................................32
Acute leukaemia...........................................................................................................................32
Common symptoms and their causes...........................................................................................33
Chronic leukaemia........................................................................................................................34
Treatment of leukaemia...................................................................................................................35
Acute leukaemia...........................................................................................................................35
Treatment choice..........................................................................................................................36
Treatment of chronic leukaemia...................................................................................................37
Immunotherapy................................................................................................................................38
New developments.......................................................................................................................39
Week 11: Itch, fever and swollen glands..............................................................................................41
Lymphadenopathy............................................................................................................................41
The lymph nodes and B-cell formation.............................................................................................41
The structure of an antibody........................................................................................................41
3
, Selection.......................................................................................................................................42
Activation of B-cells......................................................................................................................43
B-cell lymphomas.............................................................................................................................46
Classification:................................................................................................................................46
Staging of lymphoma....................................................................................................................48
IPI score........................................................................................................................................48
Follicular lymphoma.....................................................................................................................52
Diffuse large B-cell lymphoma......................................................................................................52
Diagnosis of lymphoma................................................................................................................53
R-CHOP treatment........................................................................................................................54
Post-treatment.................................................................................................................................55
Chemotherapy..............................................................................................................................55
Radiotherapy................................................................................................................................56
Secondary malignancies...............................................................................................................56
4
,Week 9: General principles of oncology and breast
cancer
Oncological language
Curative
- Free of cancer until death because of other cause
- No detectable disease after treatment
Treatment without curative intent = aim to render the patient disease-free
Curative treatment does not mean being cured!
Breast cancer 10-year survival is 90%
Pancreatic cancer survival is 15-25% 5-year survival
Palliative
When the disease cannot be cured treatment that alleviates the symptoms of a
disease (less toxicity)
o Radiotherapy for painful bone metastasis
o Oral chemotherapy to decrease liver metastasis to diminish fatigue
o Mastectomy for an ulcerative breast cancer patient with a few bone
metastasis
The surprise question: Would I be surprised if this patient died in the next year?
Survival prognosis
Some cancers become more of a chronic disease
Scoring the patient’s physical condition
Karnofsky score from 100%-0%
70% = caring for self, not being able to do normal activities or work
30% = severely disabled, hospital admission required but death is not inevitable
ECOG score
ECO Description
G
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity, but ambulatory and able to carry out
work of a light sedentary nature (e.g. light house work or office work)
2 Ambulatory and capable of selfcare, but unable to carry out any work activities (up
and about more than 50% of waking hours)
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking
hours makes it difficult to give chemotherapy because that would up the score
to 4
4 Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair
5
, 5 Dead
Primary therapy
Taking the tumour away with a curative intent
Surgery has the largest impact on survival:
- Breast cancer
- Colon cancer
- Melanoma
- Sarcoma
Sometimes radiotherapy is first-line therapy:
- Early squamous cell carcinoma of the larynx
- Some lung cancers
- Early prostate cancer
Sometimes chemotherapy in non-solid cancers: leukaemia
Local treatment = applied to the tumour site
Systemic treatment = applied to the entire body
- Chemotherapy
- Immunotherapy
- Antihormonal therapy
Adjuvant therapy
= in addition to primary therapy to prevent recurrence
- Radiotherapy after conservative breast surgery
- Radiotherapy after colon resection
Neoadjuvant therapy
= before surgery to decrease the size of the tumour and make the surgery less aggressive
Also to make the chemotherapy schedule more personalised
6
,The hallmarks of cancer
The normal cell cycle
G1 (gap) phase: growth to a normal size after mitosis
Restriction point: repression of entering a new cell cycle can only be passed if
circumstances are beneficial (e.g. enough nutrients or undamaged DNA or when
growth factors are present)
G0 phase: the cell differentiates to carry out certain functions no longer divides
Some cells can enter the cell cycle again after positive stimuli
S (synthetic) phase: DNA replication and linking of the sister chromatids
G1/S checkpoint: check for DNA damage or stalled replication forks by p53
G2 (gap) phase: key enzymes for mitosis are converted into their active forms
G2/M checkpoint: check for damaged or unduplicated DNA
M (mitosis) phase: mitosis of the cell
Most cells are in the interphase (G1 t/m S)
Self-sufficiency of growth
Normal growth: growth factor binds to receptor after stimulus is removed, growth it
stopped
Cancer cells can make their own growth stimuli due to mutations in oncogenes:
o Production of growth factors (e.g. cyclins) = autocrine stimulation
o Production of growth receptors
7
, o Mutation in downstream pathways
Insensitivity to growth inhibition
Normally: APC inhibits β-catanin when growth signal comes APC is broken down β-
catanin signals the cell to grow
In cancer cells APC is not present due to a mutation in the gene coding for it
In general: mutations in tumour suppression genes (like APC) lead to insensitivity to growth
inhibition
Evasion of apoptosis
Normally: cells with DNA damage are detected by p53 (at the G1/S checkpoint) repair or
apoptosis
Tumour cells often have a mutation in p53 no DNA repair or apoptosis
Unlimited replication
Normally: number of times a cell can divide is limited after 40-50 replication cycles, the
telomeres are gone the cell will be forced into the resting phase by p53
In tumour cells:
o P53 is often defect cell division continuous (with DNA damage)
o Activation of telomerase telomeres are lengthened infinite growth
Angiogenesis
Cells have to lie within 2 mm from the closest blood vessel otherwise hypoxia and not
enough nutrients necrosis
Tumour cells produce angiogenic factors production of a vasculature to supply
the tumour
Invasion and metastasis
Cancer cells show abnormal morphological features called dysplasia
- Slightly abnormal = low-grade dysplasia
- Moderately abnormal = middle-grade dysplasia
- Highly abnormal = high-grade dysplasia or carcinoma in situ the beginning of
cancer
The basal membrane separates the epithelial layer from the stromal compartment (contains
blood and lymph vessels)
Dysplastic cells have not (yet) invaded the stroma if they do, the tumour can
metastasise
When the tumour invades the epithelial cell layer they can invade the stroma and
metastasise = invasion
8
Neoplasms I
Summary
1
,Content
Week 9: General principles of oncology and breast cancer....................................................................5
Oncological language..........................................................................................................................5
Curative..........................................................................................................................................5
Palliative.........................................................................................................................................5
Scoring the patient’s physical condition.........................................................................................5
Primary therapy..............................................................................................................................6
Adjuvant therapy............................................................................................................................6
Neoadjuvant therapy......................................................................................................................6
The hallmarks of cancer......................................................................................................................7
The normal cell cycle......................................................................................................................7
Self-sufficiency of growth...............................................................................................................7
Insensitivity to growth inhibition....................................................................................................8
Evasion of apoptosis.......................................................................................................................8
Unlimited replication......................................................................................................................8
Angiogenesis...................................................................................................................................8
Invasion and metastasis..................................................................................................................8
Deregulating cellular energetics.....................................................................................................9
Genomic instability.........................................................................................................................9
Avoiding immune destruction/tumour enabling inflammation......................................................9
Inflammation can stimulate tumour growth:.................................................................................9
Breast caner......................................................................................................................................10
Cancer diagnostics............................................................................................................................11
Clinical signs..................................................................................................................................11
Symptoms and diagnostics of breast cancer.....................................................................................12
Basic diagnostics...........................................................................................................................12
Symptoms of early breast cancer.................................................................................................12
Symptoms of advanced breast cancer..........................................................................................13
History taking................................................................................................................................14
Mammography.............................................................................................................................14
Ultrasound....................................................................................................................................15
MRI...............................................................................................................................................15
Chest X-ray vs CT scan..................................................................................................................16
Fine needle aspiration..................................................................................................................16
Core needle biopsy.......................................................................................................................17
2
, FDG-PET/CT..................................................................................................................................17
Breast cancer imaging: CT thorax/abdomen.................................................................................17
TNM and cancer staging...................................................................................................................19
TNM..............................................................................................................................................19
UICC staging..................................................................................................................................20
Cancer treatment.............................................................................................................................21
Surgery.........................................................................................................................................21
Radiotherapy................................................................................................................................21
Systemic therapy..........................................................................................................................22
Chemotherapy..............................................................................................................................23
Immunotherapy............................................................................................................................24
Hormonal therapy........................................................................................................................24
PARP inhibitors:............................................................................................................................24
Follow-up and aftercare...................................................................................................................24
Palliative treatment and care...........................................................................................................27
Statistics...........................................................................................................................................28
Risk...................................................................................................................................................29
Case 1:..........................................................................................................................................29
Case 2:..........................................................................................................................................30
Bayesian thinking..........................................................................................................................30
Week 10: Fever, bleeding and fatigue..................................................................................................31
Haematopoiesis................................................................................................................................31
Leukaemia........................................................................................................................................32
Acute leukaemia...........................................................................................................................32
Common symptoms and their causes...........................................................................................33
Chronic leukaemia........................................................................................................................34
Treatment of leukaemia...................................................................................................................35
Acute leukaemia...........................................................................................................................35
Treatment choice..........................................................................................................................36
Treatment of chronic leukaemia...................................................................................................37
Immunotherapy................................................................................................................................38
New developments.......................................................................................................................39
Week 11: Itch, fever and swollen glands..............................................................................................41
Lymphadenopathy............................................................................................................................41
The lymph nodes and B-cell formation.............................................................................................41
The structure of an antibody........................................................................................................41
3
, Selection.......................................................................................................................................42
Activation of B-cells......................................................................................................................43
B-cell lymphomas.............................................................................................................................46
Classification:................................................................................................................................46
Staging of lymphoma....................................................................................................................48
IPI score........................................................................................................................................48
Follicular lymphoma.....................................................................................................................52
Diffuse large B-cell lymphoma......................................................................................................52
Diagnosis of lymphoma................................................................................................................53
R-CHOP treatment........................................................................................................................54
Post-treatment.................................................................................................................................55
Chemotherapy..............................................................................................................................55
Radiotherapy................................................................................................................................56
Secondary malignancies...............................................................................................................56
4
,Week 9: General principles of oncology and breast
cancer
Oncological language
Curative
- Free of cancer until death because of other cause
- No detectable disease after treatment
Treatment without curative intent = aim to render the patient disease-free
Curative treatment does not mean being cured!
Breast cancer 10-year survival is 90%
Pancreatic cancer survival is 15-25% 5-year survival
Palliative
When the disease cannot be cured treatment that alleviates the symptoms of a
disease (less toxicity)
o Radiotherapy for painful bone metastasis
o Oral chemotherapy to decrease liver metastasis to diminish fatigue
o Mastectomy for an ulcerative breast cancer patient with a few bone
metastasis
The surprise question: Would I be surprised if this patient died in the next year?
Survival prognosis
Some cancers become more of a chronic disease
Scoring the patient’s physical condition
Karnofsky score from 100%-0%
70% = caring for self, not being able to do normal activities or work
30% = severely disabled, hospital admission required but death is not inevitable
ECOG score
ECO Description
G
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity, but ambulatory and able to carry out
work of a light sedentary nature (e.g. light house work or office work)
2 Ambulatory and capable of selfcare, but unable to carry out any work activities (up
and about more than 50% of waking hours)
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking
hours makes it difficult to give chemotherapy because that would up the score
to 4
4 Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair
5
, 5 Dead
Primary therapy
Taking the tumour away with a curative intent
Surgery has the largest impact on survival:
- Breast cancer
- Colon cancer
- Melanoma
- Sarcoma
Sometimes radiotherapy is first-line therapy:
- Early squamous cell carcinoma of the larynx
- Some lung cancers
- Early prostate cancer
Sometimes chemotherapy in non-solid cancers: leukaemia
Local treatment = applied to the tumour site
Systemic treatment = applied to the entire body
- Chemotherapy
- Immunotherapy
- Antihormonal therapy
Adjuvant therapy
= in addition to primary therapy to prevent recurrence
- Radiotherapy after conservative breast surgery
- Radiotherapy after colon resection
Neoadjuvant therapy
= before surgery to decrease the size of the tumour and make the surgery less aggressive
Also to make the chemotherapy schedule more personalised
6
,The hallmarks of cancer
The normal cell cycle
G1 (gap) phase: growth to a normal size after mitosis
Restriction point: repression of entering a new cell cycle can only be passed if
circumstances are beneficial (e.g. enough nutrients or undamaged DNA or when
growth factors are present)
G0 phase: the cell differentiates to carry out certain functions no longer divides
Some cells can enter the cell cycle again after positive stimuli
S (synthetic) phase: DNA replication and linking of the sister chromatids
G1/S checkpoint: check for DNA damage or stalled replication forks by p53
G2 (gap) phase: key enzymes for mitosis are converted into their active forms
G2/M checkpoint: check for damaged or unduplicated DNA
M (mitosis) phase: mitosis of the cell
Most cells are in the interphase (G1 t/m S)
Self-sufficiency of growth
Normal growth: growth factor binds to receptor after stimulus is removed, growth it
stopped
Cancer cells can make their own growth stimuli due to mutations in oncogenes:
o Production of growth factors (e.g. cyclins) = autocrine stimulation
o Production of growth receptors
7
, o Mutation in downstream pathways
Insensitivity to growth inhibition
Normally: APC inhibits β-catanin when growth signal comes APC is broken down β-
catanin signals the cell to grow
In cancer cells APC is not present due to a mutation in the gene coding for it
In general: mutations in tumour suppression genes (like APC) lead to insensitivity to growth
inhibition
Evasion of apoptosis
Normally: cells with DNA damage are detected by p53 (at the G1/S checkpoint) repair or
apoptosis
Tumour cells often have a mutation in p53 no DNA repair or apoptosis
Unlimited replication
Normally: number of times a cell can divide is limited after 40-50 replication cycles, the
telomeres are gone the cell will be forced into the resting phase by p53
In tumour cells:
o P53 is often defect cell division continuous (with DNA damage)
o Activation of telomerase telomeres are lengthened infinite growth
Angiogenesis
Cells have to lie within 2 mm from the closest blood vessel otherwise hypoxia and not
enough nutrients necrosis
Tumour cells produce angiogenic factors production of a vasculature to supply
the tumour
Invasion and metastasis
Cancer cells show abnormal morphological features called dysplasia
- Slightly abnormal = low-grade dysplasia
- Moderately abnormal = middle-grade dysplasia
- Highly abnormal = high-grade dysplasia or carcinoma in situ the beginning of
cancer
The basal membrane separates the epithelial layer from the stromal compartment (contains
blood and lymph vessels)
Dysplastic cells have not (yet) invaded the stroma if they do, the tumour can
metastasise
When the tumour invades the epithelial cell layer they can invade the stroma and
metastasise = invasion
8
